A critical step in the development of a solid tumor is the transition of a dormant or slow growing avascular tumor into a rapidly growing metastatic vascularized tumor. This process of neovascularization depends on the ability of capillary endothelial cells to complete the following processes: hydrolysis of basement membrane around pre-existing vessels, migration toward the tumor stimulus, cell proliferation, and the formation of closed vascular channels. We have succeeded in culturing capillary endothelial cells and have used them to develop in vitro assays for the cellular components of the vascular process. These assays have been of use in the identification and isolation of tumor-derived stimulators of neovascularization and they have also been used for the detection of such factors in biological fluids from tumor-bearing individuals. In the phase of this project, we will attempt to more fully understand the factors that control the growth and migration of capillary endothelial cells by designing a defined serum-free medium for these cells and by utilizing assays that can distinguish the directional, non-directional, and adhesive components of endothelial cell motility. We also plan to explore the complex interactions between capillary endothelial cells and other motile cells such as mast cells and eosinophils that may release factors that modulate the rate and direction of new capillary growth.